Share article

Background

Contralateral tumor (CLT) occurs in 3.5-5% of men diagnosed with non-seminomatous testicular cancer.

ITGCNU (intratubular germ cell neoplasia of the unclassified type) is a precursor lesion to the development of germ cell tumor, and 50-100% of lesions transform into invasive germ cell tumor (GCT) within about 5-10 years of detection. When these lesions are detected in the contralateral testicle, aggressive therapy with radiation (doses 14 Gy- 20 Gy) to the testicle is offered to patients to reduce their risk of development of invasive GCT.

ITGCNU can only be detected by open biopsy of the contralateral testicle as these lesions do not form masses to detect with imaging or physical exam and are not associated with known serum tumor markers.

When testicular biopsies are performed, the rate of ITGCNU detection is about 5% in European patients with unilateral GCT and about 2% in North American patients with unilateral GCT. The rate of false negative results has been found to be low with adequate sampling.

Recommendation for biopsy of the contralateral testicle in patients with clinical stage I testicular cancer is controversial. Currently, the trend in Europe is to recommend biopsy in order to identify patients with the precursor lesions and offer these patients treatment with radiation therapy to the contralateral testicle.

The practice trend in North America is to defer biopsy and follow patients closely. Given the excellent response to treatment of early stage testicular GCTs, if a contralateral GCT develops, salvage therapy can often effectively eliminate the discovered malignancy.

The efficacy of adjuvant chemotherapy to reduce the incidence of bilateral cancer is uncertain.

The objective of this study was to determine effect of chemotherapy on contralateral tumor (CLT) development.

Materials and Methods

Inclusion Criteria: patients with clinical stage 1 nonseminoma GCT were included in this prospective, population-based SWENOTECA study, treated between 1995-2007.

Treatment was either adjuvant chemotherapy (1-2 courses of BEP or CVB) or surveillance, based on patient's choice. If patients had lymphovascular invasion, surveillance was not offered.

Contralateral testicular biopsy was recommended for all patients.

In case of contralateral ITGCNU, radiotherapy to 16 Gy to the testicle was recommended.

The estimated cumulative incidence of CLT was calculated using the Kaplan-Meier method. Multivariable analysis was performed to identify risk factors for metachronous cancer.

Results

Of the 988 patients enrolled in the study, 13 patients were excluded

490 patients received adjuvant chemotherapy and 485 received surveillance

With a median follow-up of 6.3 years, 29 (3.9%, 6 synchronous and 23 metachronous) patients developed CLT. The mean time to contralateral cancer was 3.7 years; 70% of these CLTs were stage 1.

Cumulative incidence of CLT was similar in biopsied patients (4.3%) and un-biopsied patients (3.0%)

Biopsies showed ITGCNU in 9/283 (3.1%) patients. All but 1 of these 9 patients received radiation therapy. There were 2 patients who developed CLT. One patient developed CLT before radiation therapy started and one patient developed CLT cancer after completing radiation therapy and chemotherapy.

The incidence of CLT was similar following adjuvant chemotherapy, 3.7 % (11/490), and surveillance, 3.1% (12/485), p=0.99.

Upon evaluating potential risk factors for metachronous cancer, young age at orchiectomy was a significant risk factor for metachronous cancer, HR 0.94 (CI: 0.89-0.99), p=0.04. The risk of CLT decreased by 6% with each year of life.

Limitations

Although contralateral testicular biopsy was recommended in all patients, it was only performed in 283 patients. There was a large amount of variation in the rate of biopsy at the 7 hospitals involved in the study, ranging from 5-70%.

The study had a relatively high rate of false negatives on biopsy. 2.5% (7/274) biopsy negative patients developed CLT.

Author's Conclusions

In this selected population, adjuvant chemotherapy did not reduce the incidence of CLT.

There was a high proportion of false negative biopsies, which might explain why biopsy negative patients had the same risk of CLT as patients not undergoing biopsy.

Young patients had the highest risk of developing contralateral cancer.

Clinical Implications

Contralateral testicular biopsy is not beneficial to patients with clinical stage I nonseminoma as the rate of CLT development is low. Additionally, there is no difference in the development of CLT in patients who received a biopsy and those who did not receive a biopsy

Radiation therapy is effective in treating ITGCNU, however, delaying radiation therapy until the development of CLT may benefit those patients who wish to preserve their fertility for as long as possible.

Based on the results presented here, chemotherapy should not be given with the goal of decreasing the risk of CLT development.